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Critical care, neurology and analgesia
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Remifentanil’s ester linkages are metabolised by nonspecific tissue and red blood cell esterases [175,176] to carbonic acid, which is renally excreted. Clearance data, expressed per kilogram, show decreasing clearance with age; 90 ml/kg/min in infants less than 2-years-old, 60 ml/kg/min between 2–12 years and 40 ml/kg/min in adults [61, 174]. Vss in children is smaller (213 ml/kg, SD 85) compared with adults (390 ml/kg, SD 250), and possibly increased in young infants (450 ml/kg) [61,174]. Remifentanil’s context-sensitive half-life is independent of infusion duration (3.2 min, SD 0.9).
Pain management
Published in Hemanshu Prabhakar, Charu Mahajan, Indu Kapoor, Essentials of Anesthesia for Neurotrauma, 2018
Additionally, it is important to understand the concept of context-sensitive half-life as this is clinically relevant when lipophilic agents are given as a continuous infusion. The context-sensitive half-life measures the decrease in the drug concentration after a constant infusion of a given duration. For example, although the terminal half-life of fentanyl after one bolus injection is approximately 1 to 2 hours, the context-sensitive half-life after a 6-hour infusion is approximately 200 minutes.29
Total Intravenous Anaesthesia
Published in Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod, The Primary FRCA Structured Oral Examination Study Guide 2, 2017
Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod
During an infusion, the plasma will have the highest concentration of the drug in the body and therefore the drug will tend to travel down its concentration gradient into various tissues until tissue and plasma concentrations reach equilibrium.If the infusion is given for long enough for plasma concentration to reach equilibrium with the tissues, there will be no net movement of the drug between compartments as long as the rate of infusion matches the rate of elimination of the drug.Tissues with a high perfusion will equilibrate with plasma faster than those with low perfusion. Tissues with a high fat content and poor perfusion will act as a store.Once a drug infusion has stopped, the drug concentration in the plasma will start to fall as the drug is metabolised and excreted.The tissues will then have a higher concentration of the drug compared with the plasma and hence drug will redistribute from these tissues into the plasma.The longer the duration of an infusion, the more drug will accumulate in the tissues, forming a store that can then replenish and maintain the plasma levels as the drug is metabolised and excreted.This results in the context-sensitive half-life.
An up-to-date overview of sublingual sufentanil for the treatment of moderate to severe pain
Published in Expert Opinion on Pharmacotherapy, 2020
Susanna Porela-Tiihonen, Hannu Kokki, Merja Kokki
Duration of analgesia is largely determined by the time for the sufentanil plasma concentration to decrease from Cmax to 50% of Cmax after discontinuation of dosing, a context-sensitive half-life. After either a single dose or multiple doses hourly over 12 hours, the median context-sensitive half-life is 2.3 hours demonstrating predictable and consistent duration of action after multiple dosing of the sublingual tablet [26,27].